Polyvalent DNA gold nanoparticles, now more commonly referred to as spherical nucleic acids, (Fig. 1) are colloidal gold particles densely modified with short (typically ~30-mer or less), highly oriented, synthetic DNA strands. They were invented by Chad Mirkin et al. at Northwestern University in 1996. Paul Alivisatos et al. at the University of California, Berkeley introduced a related monovalent structure the same year. Due to the strong interaction between gold and thiols (-SH), the first polyvalent DNA gold nanoparticles were obtained by capping the gold nanoparticles with a dense monolayer of thiol-modified DNA. The dense packing and negative charge of the phosphate backbones of DNA orients it into solution (like a “koosh ball”) with a footprint that is dependent on factors including